The transcriptome is the complete set of transcripts in a cell, and their quantity, for a specific developmental stage or physiological condition. Understanding the transcriptome is essential for interpreting the functional elements of the genome and revealing the molecular constituents of cells and tissues, and also for understanding development and disease. The key aims of transcriptomics are: to catalogue all species of transcript, including mRNAs, non-coding RNAs and small RNAs; to determine the transcriptional structure of genes, in terms of their start sites, 5′ and 3′ ends, splicing patterns and other post-transcriptional modifications; and to quantify the changing expression levels of each transcript during development and under different conditions.
Recently, the development of novel high-throughput DNA sequencing methods has provided a new method for both mapping and quantifying transcriptomes. This method, termed RNA-Seq (RNA sequencing), has clear advantages over existing approaches and is expected to revolutionize the manner in which eukaryotic transcriptomes are analysed. It has already been applied to Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, mouse and human cells.
Prostate cancer is the most commonly diagnosed malignancy among men in the USA, and is the second most common cause of cancer mortality in that group. It is estimated that one in six American men will receive a diagnosis of prostate cancer at some point in their lives, at an average age of 68 years. In 2010, there were 217,730 newly diagnosed cases and 32,050 deaths from prostate cancer in the USA alone.
The management of advanced and metastatic disease, however, is more difficult and requires systemic treatment with either hormonal (i.e., androgen deprivation) therapy (ADT) or chemotherapy. Since androgens are the main regulators of prostate cancer growth, the rationale for ADT is that tumor cells deprived of key hormonal growth regulators will either undergo apoptosis or survive in an arrested state in the G1 phase of the cell cycle. The median duration of response to ADT is approximately 18-24 months, after which most patients progress to a more aggressive form of disease termed castration (hormone)-resistant prostate cancer (CRPC).
The outlook for patients with CRPC is quite grim. Several investigators have reported that, without treatment, median survival time ranges from 9.1 to 21.7 months. CRPC is now the second most common cause of male cancer-related mortality. However, recent discoveries pertaining to the biology and pathophysiology of the disease over the last two decades have enabled the development of new therapeutic modalities with the hope of improving those statistics. In recent years, a select few chemotherapy, hormonal, immunotherapy and palliative agents have gained US FDA approval for use in patients with CRPC. Additionally, many experimental anticancer drugs are in development, and there are numerous ongoing clinical trials seeking to elucidate optimal treatment regimens using existing modalities that maximize survival time while minimizing side effects.
Genetic profiling of circulating tumor cells (CTCs) in subjects with CRPC would greatly help diagnosis and identify specific treatment regimens for the subjects. The genomic profile of CTCs from prostate cancer (PCa) are poorly identified due to the rarity of CTCs and the challenge in isolating them.